稀土配合物荧光探针在活细胞成像研究中的新进展

稀土配合物荧光探针在生物学研究中,尤其在活细胞成像方面的应用渐已引起人们的关注.本文就稀土配合物的发光特点及其作为荧光探针在活细胞成像研究领域的进展进行了评述.引用文献70篇.     

发光金属Salen配合物作为检测细胞内微黏度的荧光成像探针

细胞内微黏度是描述细胞状态的重要物理参数,与物质转运和信号转导等一系列扩散控制的生理过程密切相关.构筑对细胞内微黏度响应灵敏的荧光探针是原位实时检测细胞状态的重要手段之一.我们设计含有D-π-A推拉电子结构N,N'-双水杨醛缩乙二胺类配体(N,N'-thiophene-3,4-bis-4'-(diethylamino)-salicylimine,Salen)的Zn~(2+)和Al~(3+)配合物,考察了其光物理性质,发现该类配合物具有对溶液黏度依赖的荧光增强性质.同时,相比于配合物ZnSalen,[AlSalen]~+Cl~-具有检测灵敏度高、荧光成像信号增强倍数高等优点.利用激光扫描共聚焦荧光成像和荧光寿命成像,[AlSalen]~+Cl~-同样表现出在培养温度降低或细胞自噬下的荧光增强和发光寿命延长等变化,显示其作为检测细胞内微黏度荧光探针的潜在应用价值.     

糖基聚集诱导发光材料的研究进展

聚集诱导发光材料具有优异的光学性质,在传感检测等领域具有广泛用途.由于大部分聚集诱导发光类荧光基团具有很强的疏水性,一定程度上限制了其应用范围.近五年,基于糖类分子结构多样和水溶性好的优势,我们课题组将多种糖类物质和聚集诱导发光分子偶联,制备出一系列糖基聚集诱导发光材料.该类材料有很好的水溶性和生物相容性,能够降低背景荧光和生物毒性.通过和目标检测物结合或者反应,实现了对多种生物活性分子的荧光检测和细胞成像.本文综述了近年来糖基聚集诱导发光材料领域的重要研究进展,以进一步拓展聚集诱导发光材料的应用领域,为生物活性物质功能监测和糖化学生物学的研究等提供有效的研究工具.     

一种基于查尔酮衍生物的荧光探针对巯基氨基酸的检测及细胞成像

生物硫醇(如半胱氨酸(Cys)、同型半胱氨酸(Hcy)及谷胱甘肽(GSH))与生物体和细胞中的许多生理和病理过程密切相关。荧光探针是对生物硫醇灵敏检测与成像的有力工具。本文合成了一种可检测生物硫醇的基于2′-羟基查尔酮荧光团开启型荧光探针1。探针中的2,4-二硝基苯磺酸酯基团既作为反应识别基团,又作为荧光猝灭基团。在DMSO/Tris(体积比8/2,pH=8.4)中,探针1与生物硫醇反应后释放出前体化合物3,3具有激发态分子内质子转移(ESIPT)和聚集诱导发光(AIE)特性,从而导致长波长荧光发射及较大的斯托克斯位移。探针1具有合成简单、灵敏度高、选择性高、细胞毒性低等优点,可以方便地检测溶液和活细胞中的生物硫醇。     

基于聚集诱导发光荧光探针的细胞成像研究进展

荧光探针是化学传感技术领域在20世纪末的一项重大发现,具有合成简单、灵敏度高、选择性好、响应时间短、可视化高等优点。 将具有聚集诱导发光现象(AIE)特征的荧光基团与具有生物相容性的高分子结合起来,使得荧光材料具有毒性低、光稳定性好、生物相容性好等特点。 在分子、离子检测和细胞成像技术中得到广泛的研究和应用。 本文综述了细胞质成像、细胞膜成像、线粒体成像、溶酶体成像、脂滴成像、细胞核成像、细胞核和线粒体双靶向性成像的荧光探针,并对其应用前景做了展望。     

四苯乙烯衍生物与大环主体在主客体相互作用下的聚集诱导发光

具有聚集诱导发光性质化合物的发展不仅很大程度上解决了传统有机分子发色团在高浓度、固态或者薄膜等形式的聚集状态下荧光猝灭的问题,而且扩展了有机发色团在荧光探针、传感器以及细胞成像等方面的应用。其中,四苯乙烯及其衍生物作为具有聚集诱导发光性质的典型化合物已被广泛应用在材料化学、生物化学等相关研究领域。受此启发,超分子化学家也将这类具有聚集诱导发光性质的四苯乙烯及其衍生物作为研究对象引入到超分子化学的领域,特别是利用大环主体与四苯乙烯客体通过主客体相互作用有效地限制了荧光客体分子的分子内转动或运动,增强了这类超分子体系的发光强度,并为其在刺激响应性传感器、智能探针等方面提供了新思路。本文总结了近年来涉及四苯乙烯衍生物与大环主体通过主客体相互作用形成聚集诱导发光超分子体系的发展,并按照大环主体进行分类简要介绍其应用。     

聚集诱导发光探针用于细胞缺血再灌注诱导过氧化氢成像研究

过氧化氢是一种重要的内源性信号分子,参与调控多种生理和病理过程.缺血再灌注会诱导产生大量内源性过氧化氢,对细胞和组织造成严重损伤.聚集诱导发光探针能够规避常规荧光团浓度过大所引起的聚集荧光淬灭的问题.以4-乙烯吡啶修饰的四苯乙烯为荧光基团,苯硼酸为过氧化氢识别基团,设计合成了一种具有聚集诱导发光性质的长波长过氧化氢荧光探针.光谱测试结果表明,探针对过氧化氢具有较好的选择性和较高的灵敏度,最低检测限为6.9×10^-8mol/L.共聚焦成像结果表明,探针具有较好的细胞通透性,可用于糖氧剥夺再灌注诱导HeLa细胞和脂多糖诱导斑马鱼内源性过氧化氢生成研究.     

基于1,8-萘酰亚胺的多分析物荧光探针的构建和应用

生命受细胞内复杂的代谢过程控制。科学界正在进行的努力之一是研究和理解这些动态生化反应以及生物分子在维持生命中的作用。荧光探针具有操作简单、成本低、灵敏度高、可在活体中多通道和实时可视化等优点,已被广泛用于分析物在生理和病理过程中的可视化研究。然而,多数荧光探针只可响应单分析物,不适于复杂生物体系中多分析物的分析检测。近5年来,以1,8-萘酰亚胺为荧光报告基团的多分析物荧光探针在生物或环境领域得到了快速的发展。依据探针荧光发光机制,本文将其分为单发光机制(PET、ICT和FRET)、双发光机制(PET-ICT、PET-FRET和ICT-FRET等双机制协同作用)等方式,综述了国内外基于1,8-萘酰亚胺的多分析物荧光探针在设计策略、识别过程、光学性质和细胞成像等方面的新进展,并对此类荧光探针的发展趋势和挑战进行了展望。     

单细胞核酸编码扩增成像分析

单细胞成像可在单细胞水平观测目标物位置、 确定目标物含量, 在生命科学与临床医学研究领域应用广泛. 核酸编码扩增技术利用特定分子反应将待测目标识别转化为核酸条码的扩增, 具有探针种类多、 易编程、 反应条件温和及信号放大效率高等特点, 在单细胞低丰度、 高灵敏、 多目标物成像中优势显著, 为理解细胞状态、 探索生命过程提供了新思路. 本文综合评述了核酸编码扩增在单细胞荧光成像领域的研究进展, 以目标物的编码方式为分类依据, 系统阐述了固定细胞原位成像和活细胞成像中不同目标物编码与扩增成像方式的区别, 并对活细胞成像中多重检测面临的问题以及未来发展前景进行了展望.     

基因编码荧光探针的构建与应用

基因编码荧光探针能够可视化探测活细胞中多种分析物及其相关分子事件,已成为细胞生物学等生命科学研究的强大分子工具.本文介绍了基因编码荧光探针的类型和主要应用场景,归纳了现有探针的优点和存在的问题,并对其未来发展进行了展望.     

Oxygen imaging of living cells and tissues using luminescent molecular probes

Oxygen imaging of biological cells and tissues is becoming increasingly important in cell biology and in the pathophysiology of various hypoxia-related diseases. The optical oxygen-sensing method using luminescent probes provides very useful, high spatial resolution information regarding oxygen distribution in living cells and tissues. This review focuses on recent advances in biological oxygen measurements based on the phosphorescence quenching of probe molecules by oxygen, and on hypoxia-sensitive fluorescent probes. Special attention is devoted to metal complex probes, Pt(II)- and Pd(II)-porphyrins, Ru(II) complexes, and Ir(III) complexes. Current knowledge regarding the mechanism of phosphorescence quenching of metal complexes by oxygen is described in relation to the oxygen sensitivity of the probes, and recent advances in optical oxygen probes and detection techniques for intracellular and tissue oxygen measurements are reviewed, emphasizing the usefulness of chemical modifications for improving probe properties. Tissue oxygen imaging and hypoxic tumor imaging using these metal complex probes demonstrate the vast potential of optical oxygen-sensing methods using luminescent probes.     

Design of luminescent iridium(III) and rhenium(I) polypyridine complexes as in vitro and in vivo ion,molecular and biological probes

Many luminescent transition metal polypyridine complexes display intense and long-lived triplet charge-transfer and intraligand transition emission with a large Stokes’ shift. These properties render them promising candidates as luminescent probes for ions, DNA, peptides, proteins and other biological entities. In this review article, we have summarised recent reports on ion, molecular and biological probes derived from luminescent rhenium(I) and iridium(III) polypyridine complexes. These complexes have been appended with different recognition moieties that interact with ions and biological molecules. The recognition is reflected by a change of spectroscopic and/or photophysical properties of the probes. The use of these complexes as cellular probes and imaging reagents has also been discussed.     

Applications of luminescent inorganic and organometallic transition metal complexes as biomolecular and cellular probes

The rich photophysical properties of luminescent inorganic and organometallic transition metal complexes, such as their intense, long-lived, and environment-sensitive emission, render them excellent candidates for biological and cellular studies. In this Perspective, we review examples of biological probes derived from luminescent transition metal complexes with a d(6), d(8), or d(10) metal center. The design of luminescent covalent labels and noncovalent probes for protein molecules is discussed. Additionally, the recent applications of these complexes as cellular probes and bioimaging reagents are described. Emphasis is put on the structural features, photophysical behavior, biomolecular interactions, cellular uptake, and intracellular localization properties of luminescent transition metal complexes.     

Tris(Znsalen) cryptand minimizes Znsalen aggregation arising from intermolecular Zn…O interaction

Exploring the factors to control Znsalen aggregation is of importance to design functional materials in catalysis, optical materials and biological imaging. In this work, we synthesized and characterized four cryptand type triZnsalen complexes and found that cryptand structure could efficiently minimize intermolecular Zn···O interaction. More importantly, encapsulated by PLGA nanoparticles, cryptand triZnsalen 1 displayed visible intracellular fluorescence whereas monomeric Znsalen 5 could not. These results provide a new access to design new luminescent materials with the potential application in optics and biological studies.     

Engineering emissive europium and terbium complexes for molecular imaging and sensing

Emissive f-block coordination complexes constitute an important class of optical probes, with applications ranging from sensing of bioactive species, high throughput assays and screening protocols in vitro, to time-resolved imaging studies in cellulo or in vivo. The key chemistry issues to be addressed in complex design and characterisation are defined, with an emphasis on the use of emissive europium and terbium complexes and their conjugates in molecular imaging. Both luminescent 'tags' useful in energy transfer studies and 'responsive' systems for sensing are discussed.     

Bioactive Luminescent Transition‐Metal Complexes for Biomedical Applications

The serendipitous discovery of the anticancer drug cisplatin cemented medicinal inorganic chemistry as an independent discipline in the 1960s. Luminescent metal complexes have subsequently been widely applied for sensing, bio‐imaging, and in organic light‐emitting diode applications. Transition‐metal complexes possess a variety of advantages that make them suitable as therapeutics and as luminescent probes for biomolecules. It is thus highly desirable to develop new luminescent metal complexes that either interact with DNA through different binding modes or target alternative cellular machinery such as proteins as well as to provide a more effective means of monitoring disease progression. In this Review, we highlight recent examples of biologically active luminescent metal complexes that can target and probe a specific biomolecule, and offer insights into the future potential of these compounds for the investigation and treatment of human diseases.     

Development of responsive lanthanide-based magnetic resonance imaging and luminescent probes for biological applications

Lanthanide complexes have unique chemical characteristics compared with typical organic complexes, and have recently attracted much interest because of the expanding need for new bioanalytical sensors. For example, magnetic resonance imaging (MRI) permits noninvasive three-dimensional imaging inside opaque organisms, and gadolinium ion (Gd(3+)) complexes have become important tools as MRI contrast agents. However, most of them are nonspecific, and report solely on anatomy. Therefore, responsive MRI contrast agents, so-called "smart" MRI contrast agents whose ability to relax water protons is greatly enhanced by recognition of a particular biomolecule, have great potential for elucidating biological phenomena. On the other hand, lanthanide complexes such as europium (Eu(3+)) and terbium (Tb(3+)) complexes have excellent luminescence properties for biological applications, i.e., long luminescence lifetime of the order of milliseconds and a large Stoke's shift of >200 nm. Their long-lived luminescence is especially suitable for time-resolved measurements, because the interference from short-lived background fluorescence and scattered light rapidly decays to a negligible level after a pulse of excitation light is applied, and the emitted light can be collected after an appropriate delay time. These luminescent lanthanide complexes have already found commercial use as highly sensitive luminescent probes in heterogeneous and homogeneous assays. This paper reviews our research on the design and synthesis of responsive lanthanide-based MRI and luminescent probes for advanced bioimaging.     

Metal–Carbonyl Units for Vibrational and Luminescence Imaging: Towards Multimodality

Metal–carbonyl complexes are attractive structures for bio‐imaging. In addition to unique vibrational properties due to the CO moieties enabling IR and Raman cell imaging, the appropriate choice of ancillary ligands opens up the opportunity for luminescence detection. Through a classification by techniques, past and recent developments in the application of metal–carbonyl complexes for vibrational and luminescence bio‐imaging are reviewed. Finally, their potential as bimodal IR and luminescent probes is addressed.     

Chemical design of nanoparticle probes for high-performance magnetic resonance imaging

Synthetic magnetic nanoparticles (MNPs) are emerging as versatile probes in biomedical applications, especially in the area of magnetic resonance imaging (MRI). Their size, which is comparable to biological functional units, and their unique magnetic properties allow their utilization as molecular imaging probes. Herein, we present an overview of recent breakthroughs in the development of new synthetic MNP probes with which the sensitive and target-specific observation of biological events at the molecular and cellular levels is possible.     

Biomedical applications of macrocyclic ligand complexes

Macrocyclic chelators can form highly stable complexes with transition metals and lanthanides. In this review, the recent advances towards biomedical applications of macrocyclic complexes are outlined. The use of such complexes in imaging as MRI contrast agents, radiopharmaceuticals and luminescent probes is discussed. The considerable scope for future development of novel metal based therapeutics based on protein binding, targeting of radioisotopes or dual function agents is also highlighted.